Year: 2023
Type: conference-abstract
Abstract: mRNA vaccines have shown high efficacy in preventing severe COVID-19, but breakthrough infections, emerging variants and waning antibody levels have warranted the use of boosters. Although mRNA boosters have been widely implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we observed that lower spike-specific antibody levels before boost were associated with higher fold-increase in spike-specific antibody levels after boost, suggesting that pre-existing antibodies to SARS-CoV-2 downmodulate the immunogenicity of mRNA-based vaccines. Similar effects were observed in mice that received mRNA-based SARS-CoV-2 vaccines and HIV-1 vaccines. Our subsequent studies in mice show that pre-existing antibodies against the antigen encoded by the mRNA vaccine itself accelerate the clearance of vaccine antigen following a booster vaccination, via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses. These data suggest that transient downmodulation of antibody effector functions may improve the efficacy of mRNA boosters against SARS-CoV-2 and other diseases. Start-up chart string, Northwestern University National Institute on Drug Abuse (NIDA, DP2DA051912)
Source: The Journal of Immunology
Institutions: Northwestern University, University of Illinois Chicago
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4385695708